Diagnostics

All cancers share certain characteristics, such as abnormal cell growth, with the potential to invade and spread to other parts of the body. While certain features are consistent across all cancers, each cancer is distinct due to its unique composition, molecular signature, and sensitivity to therapeutics. Developing tools to select a therapy specific to an individual’s cancer would be beneficial for determining the best course of treatment for that patient. Merrimack is committed to changing the landscape of cancer treatment by developing our investigational therapeutics with companion diagnostics, an approach intended to better identify patients most likely to respond to a specific therapy.

For our nanoliposomal products, the first step to developing a predictive diagnostic is to understand the unique tumor delivery properties of nanoliposomes. By coupling this knowledge with advanced imaging techniques and computational analysis, we are developing the tools to evaluate the potential and effectiveness of liposomal delivery to the tumor.  If these tools provide useful information to predict patient responses, clinicians may therefore be able to use them to better select patients who may benefit from liposomal therapy.

For our antibody-based therapeutics, we are relying on our systems biology core, validated by laboratory studies, to understand how signaling pathways affect tumor sensitivity and resistance to specific anticancer therapies. With this knowledge, we are seeking to identify tumor biomarkers which may be used to identify patients likely (or unlikely) to respond to a specific therapy.

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Positron emission tomography/computed tomography (PET/CT) of patients administered MM-302 and 64Cu-labeled MM-302 indicates liposomal accumulation in metastatic lesions. Patients were imaged within the first hour and approximately 24 to 48 hours later. A region of interest (ROI) encompassing the site of a brain metastasis, as determined by MRI, is shown. PET signal enhancement at 44 hours indicates 64Cu-MM-302 deposition. San Antonio Breast Cancer Symposium 2013

Example: An imaging diagnostic for nanoliposomal therapies

Merrimack is developing a novel imaging agent to serve as a diagnostic for our nanoliposomal product candidates. This agent has similar composition and tumor delivery properties to our nanoliposomal product candidates; however, instead of containing an active therapeutic, the liposome is loaded with a radioactive label. Using imaging and computational analysis, we plan to measure the extent of nanoliposome delivery to a patient’s tumor. Our intention is to co-develop this diagnostic agent with our nanoliposomal products, with the goal of identifying patients with tumors that are more accessible to nanoliposomal therapy.

Example: A diagnostic strategy for Merrimack’s engineered antibodies

Clinical studies of MM-121, a human monoclonal antibody designed to target the ErbB3 receptor, were conducted with a strong translational component. In recently presented Phase 2 trials, Merrimack analyzed historical and fresh tumor samples from patients for a pre-specified set of biomarkers, which we believe has the potential to identify patients who would most likely benefit from the drug. These biomarkers were selected based on preclinical research and computational modeling of the ErbB pathway. With the biomarker data from these tumor samples, we have further insight into the critical signaling pathways responsible for tumor growth and resistance to standard of care therapies.

Six Phase 2 clinical trials studying MM-121 in a variety of indications have been completed to date. Within these results, Merrimack has found that the expression of heregulin, the principal ligand that binds to and activates the ErbB3 receptor, seems to be associated with poor response to standard of care therapy for patients with platinum-resistant ovarian cancer, ER/PR+ HER2- breast cancer and EGFR wild-type non-small cell lung cancer. Heregulin-driven drug resistance pathways were found to be active in approximately 38-54 percent of patients tested. These findings may aid in advancing MM-121 into definitive studies that will allow us to prospectively screen patients for heregulin, and to also use our diagnostic assays in future clinical studies for our other antibody therapies.